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What is that?!Common Dermatologic Conditions and

How to Treat Them

Matthew Fox, MD

Assistant Professor, Division of DermatologyDell Medical School, University of Texas at Austin

Director of Dermatologic Surgery, Seton Healthcare Family

Classes of Dermatologic Medications● Topical Immune Suppressants● Immune Suppressants ● Vitamin D Derivatives ● Antibiotics, Antivirals, Antiparasitic ● Retinoids● Antimalarials● Biologic Agents ● Chemotherapeutic agents

Approach to Dermatologic Conditions

AcneInfectious diseases of the SkinEczemaPsoriasisSun Damage / Actinic Keratoses

• Know the clinical subtypes of acne *Know the mechanism and recommended dosing of topical retinoids, oral antibiotics and oral retinoids in the management of acne

• Understand the clinical presentation cutaneous dermatophyte infection

*Know the classes and recommended dosing of antifungal treatments

• Recognize the clinical manifestations of dermatitis*Know the relative potencies, side effects and indications of topical steroids

• Describe the classic clinical findings for psoriasis *Know the mechanism of action and side effects of systemic antipsoriatic medications

• Know the pertinent history and physical exam findings associated with a diagnosis of skin cancer, including the ABCDEs of melanoma

Learning Objectives

Fundamentals

• All medications have side effects• Always consider drug interactions,

including with food and supplements• Always consider pregnancy and lactation

status

If you advise the patients of side effects ahead of time, you are informing the patient.

If you did not tell the patient about a known side effect until after they experience that side effect, it is an excuse

Words to the wise…

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Reference:

• Wolverton SE, ed. Comprehensive Dermatologic Drug Therapy, 2nd Ed. Elsevier, 2007.

Approach to Dermatologic Conditions

AcneInfectious diseases of the SkinEczemaPsoriasisSun Damage / Actinic Keratoses

Topical Retinoids

• Small molecule hormones that activate nuclear receptors and regulate gene transcription

Retinoid RAR-α RAR-β RAR-γ RXR-α RXR-β RXR-γ

All-trans retinol - - - - - -

All-trans retinoic acid ++ ++ ++ - - -

Adapalene Weak ++ ++ - - -

Tazarotenicacid + +++ ++ - - -

Alitretinoin +++ +++ +++ ++ ++ ++

Bexarotene - - - +++ +++ +++

Retinoids: Clinical Effects

• Affect pathways involved in: – Inflammation– Cellular differentiation– Apoptosis – Sebaceous gland differentiation

***NORMALIZATION OF FOLLICULAR EPITHELIAL DIFFERENTIATION AND KERATINIZATION***

Adapalene

• Mild comedonal acne• 0.1% gel• Apply QHS• OTC (2016)• Pregnancy: C

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Tretinoin

• Supplied as 0.025%, 0.05%, 0.1% cream or as 0.01 - 0.1% gel

• Apply QHS• May need to start with lesser frequency • Pregnancy: C

Tazarotene

• 0.05% and 0.1% cream and gel• Apply QHS• For female patients, begin during menses• Pregnancy: X

Topical AntibioticsName Comments

Benzoylperoxide

Beneficial effectscanbeneutralized withsimultaneous tretinoinNoassociation with induction ofbacterial resistance

Clindamycin Goodgram +andanaerobiccoverage

Erythromycin Resistance tosomeP.acnes;mostbenefit isviaanti-inflammatoryeffects

Metronidazole Coverageofbothaerobicandanaerobic bacteria(morefor rosacea)

Azelaicacid Broadcoverage;goodforpigmentary disorders; OKduring pregnancy

Sodiumsulfacetamide

Broad coverageandmultiple indications

Clindamycin• Reversibly binds 50s subunit of ribosomal

RNA subunit à inhibition of protein synthesis• Broad spectrum(S. aureus, streptococci, P.

acnes)• 1% lotion or solution, applied daily to BID• Pustules, inflammatory acne >> non-

inflammatory lesions

Azelaic acid

• Activity against tyrosinase• Safe during pregnancy (B)• Supplied as 15% gel

Sodium sulfacetamide

• Commonly incorporated in formulation with sulfur

• Inhibition pro-inflammatory enzymes• Supplied as lotion for BID application

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Benzoyl peroxide

• Keratolytic and comedolytic properties• Bactericidial, broad spectrum• Broad range of concentrations (2.5-10%)

and vehicles (washes, lotion, gel, cream)• Little to no induction of bacterial resistance• Peeling, erythema, dryness

Combination products

• Improved patient adherence• Better results that individual agents alone• Many combinations:

– BPO/Clindamycin combinations– Clindamycin/retinoid combinations

Oral antibiotics

• Tetracyclines• Trimethoprim/sulfonamide• Clindamycin

Tetracyclines• Bacteriostatic, inhibit

bacterial protein synthesis• Bind 30S ribosomal subunit• Do not give to children < 9

– bone, teeth development• Pregnancy category D

Minocycline• Supplied: 50, 75, 100 mg• Dosage: 50-200 mg per day (dosed daily or BID) • Common SEs:

– Dizziness– Headache (pseudotumor cerebri)– GI– Photosensitivity– Pigmentation change– Hepatotoxic

• Not to be used in pregnancy, kids• Not to be used with isotretinoin: increased risk of

pseudotumor cerebri (applies to all tetracyclines)

Doxycycline• Supplied: 20, 50, 75, 100 mg• Dosage: 50-200 mg per day (dosed daily or BID) • Common SEs:

– GI (burning, discomfort, nausea, vomiting)• Relieved if taken with food (NON DAIRY)

– Photosensitivity– Headache– Pigmentary change– Hepatotoxic

• Not to be used in pregnancy, kids• Not to be used with isotretinoin: increased risk of

pseudotumor cerebri (applies to all tetracyclines)

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Oral retinoids - Isotretinoin• Approved for severe recalcitrant nodular

acne– Inflammatory lesions greater than 5mm in

diameter– Unresponsive to conventional tx (oral abx)

• Consider impact of disease on patient!

Isotretinoin

• Dosage:– Weight based dosing– 0.5-1 mg/kg daily, until a total cumulative dose

of 120-150 mg/kg is reached • Rate of success approx 70%

– Relapses more likely to respond to conventional treatment

ADVERSE EFFECTSTeratogenicity-Retinoic acidembryopathy

Hepatic-Elevatedtransaminases

Ocular-Reduced nightvision-Dryeyes, infection

OtherEndocrine-Hypothyroidism

Bone-Diffuseskeletalhyperostosis-Premature epiphyseal closure

Hematologic-Leukopenia-Agranulocytosis

Lipids-Elevatedcholesterol, TG

Neuro/Psych-Depression, pseudotumor

Gastrointestinal-Inflammatorybowel disease flare-Pancreatitis

Muscle-Myalgias

Alternative acne treatment

• For ‘hormonal’ acne, may consider– Spironolactone

• SE: Teratogenic, K+ monitoring– OCPs

Acne Pearls• For acne on the trunk, it is difficult for patients

to apply lotions, gels. Use washes and oral antibiotics.

• For medications to work, it takes time. Advise that the earliest they will see improvement is 6-8 weeks.

• Often need combination of products• May need oral retinoids sooner than later!

Approach to Dermatologic Conditions

AcneInfectious diseases of the SkinEczemaPsoriasisSun Damage / Actinic Keratoses

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WartsTreatment Comments

Salicylic Acid Keratolytic; consider40%plasterunderocclusion

Podophyllin Antimitotic agent;contraindicated inpregnancy;applied inoffice

Cantharidin Vesiculating agent;applied inoffice

Imiquimod Immunostimulatory (activatesTLR-7); applyatbedtime threetimesweeklyonnon-consecutivedays(genitalwarts)

CandidaAntigen

Immunostimulatory, injected into lesion

Impetigo

• Mupirocin• Staph directed antibiotic coverage

– Bactrim– Clindamycin– Doxycycline– Cephalosporins

Mupirocin• Inhibits bacterial isoleucyl-tRNA synthetase à inhibits bacterial RNA and cell wall synthesis

• Excellent coverage against S. aureus, S. epidermidis, S.pyogenes, B-hemolytic Streptococci

• ? Resistance• 2% ointment, to be applied BID• SE: burning, itching, contact dermatitis

Acyclovir / valacyclovir

• Guanosine analog• Requires phosphorylation by herpes

specific thymidine kinase• Once active, inhibits viral DNA polymerase• Valacyclovir is oral prodrug• Exceptionally safe and well tolerated

Herpes viruses• Topical acyclovir

– Supplied as 5% ointment for limited disease – low efficacy– applied Q3 hours, 6x/day for 7 days

• Acyclovir– Supplied as oral suspension– Example doses:

• Cold sore: 400 mg 5x/day for 5 days• Shingles: 800 mg 5x/day for 7-10 days

• Valacyclovir– Easier dosing, possible benefit for PHN

• Cold sore: 2g twice daily for one day• Shingles: 1g TID x 7 days

Scabies Treatments• Permethrin:

– MOA: acts on arthropod cell wall by disabling sodium transport à mite paralysis

– Applied from neck to, not just visibly affected sites– Two overnight applications separated by one week– All partners and close contacts should be treated– Reasonable to wash clothes and linens concurrent

with treatment– Pruritus may last for up to 1 month after treatment!

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Scabies Treatments• Sulfur:

– time honored– 6% precipitated sulfured, compounded, applied

daily until improved• Ivermectin:

– MOA: blocks glutamate gated chloride ion channels à paralysis of arthropod/helminth

– Off label: single 100-200 μg/kg dose or two full doses separated by one week

Azole antifungalsMOA: Inhibition of 14α-demethylase, leading to decreased ergosterol formation

Examples include:

• Ketoconazole– 2% cream, applied BID until improved– 1-2% shampoo, used in seborrheic dermatitis

• Econazole– 1% cream, applied BID until improved

• Efinaconazole– 10% topical solution, painted topically to nails once daily for 48 weeks!

Terbinafine

• Allylamine, disrupts fungal cell wall via inhibition of squalene epoxidase

• Highly lipophilic (high concentration in stratum corneum, hair follicles, sebum)

• 1% gel, cream, spray – applied daily to BID

Oral terbinafine• Severe or resistant fungal infection• 250 mg daily for:

– 2 weeks (tinea corporis)– 6 weeks (fingernails)– 12 weeks (toenails)

• Common SEs: HA, GI• Baseline LFTs and 6wks after rx starts• Needs dose adjustment in renal/liver disease• Pregnancy category: B

Regimens for tinea versicolor

• Topical zinc pyrathione wash• Topical ketoconazole wash• Topical selenium sulfate wash• Oral ketoconazole option

– Take 400mg, work up a sweat, don’t shower for at least 4 hours

Approach to Dermatologic Conditions

AcneInfectious diseases of the SkinEczemaPsoriasisSun Damage / Actinic Keratoses

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Eczema/Dermatitis

• Nonspecific term for a histologic finding– Acute—e.g. poison ivy, contact dermatitis– Subacute—e.g. atopic dermatitis– Chronic—e.g. lichen simplex chronicus

• Usually ill-defined scaly papules and plaques, except for contact dermatitis

Approach to Dermatitis• Liberal application of emollients• Remove allergens and avoid

sensitizers• Topical / oral antibiotics to

reduce secondary infection & colonization

• Topical immune suppression• Systemic immune suppression

Dermatitis NOS Treatment

• Topical immune suppression is the mainstay of treatment– Topical steroids– Topical CNIs

• For severe cases, can consider wet wraps, UV light, immunomodulators

Topical steroids• Ranked according to

strength, based on vasoconstrictor assays and blinded studies– Class 7 (least potent)

to – Class 1 (ultra potent)

Topical steroids

• Common SEs: Thinning of skin, atrophy, striae, telangiectasia, ecchymosis, may burn/sting on application (fades after 10 min)

• Don’t use every day for months and months!• Commonly used as: BID x 2 weeks then BID

on weekends only – Emphasize intermittent therapy to avoid

tachyphylaxis, atrophy etc.

Topical steroids – Base• Ointment vs. Cream vs. Solution vs. Gel vs. spray• Ointments are greasy, but penetrate better and

have fewer potential irritants• Creams rub in better and are often preferred for

small areas; creams bases have potential irritants• Solutions are used for the scalp (seborrheic

dermatitis, scalp psoriasis)• Gels are like thick solutions; Gels and alcohol-

based sprays evaporate and concentrate medications

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• Low potency: – desonide,

hydrocortisone 2.5%• Medium potency:

– triamcinolone 0.1%

• High potency: – clobetasol,

betamethasone

Topical steroids

In general, applied BID forup to 2-3 weeks as needed, then tapered…

Topical calcineurin inhibitorsTacrolimus and pimecrolimus

• Block T cell activation and proliferation– FKBP/NFAT pathway

• Often used in eczema• Particularly good for thin-skinned areas: face, eyelids,

axillae, groin• Can combine with topical steroid use

– Example: use steroid BID on weekends and TCI Monday-Friday

• However….

Possible adverse events• Possible risk of lymph node or skin

cancer:The potential for systemic immunosuppression is unknown and the role of TCI in the development of the cancer-related events in the indiv idual patient reports is also uncertain at this. Animal studies have showed that skin tumors formed faster in animals treated with tacrolimus, the active ingredient in Protopic, and exposed to light. Because of this, you should limit exposure to natural or artific ial sunlight, such as sunlamps or tanning beds.

• Viral infections: TCI use may increase the chance of getting chicken pox, shingles, or other v iral infections.

Oral steroids

• Produce apoptosis of T cells, eosinophils, downregulation of pro-inflammatory cytokines

• Often used for acute dermatitis flares• Example: Poison Ivy

– Prednisone 1 mg/kg (generally 40-60 mg), tapered slowly over 2-3 weeks

Oral steroids

• Also used for rarer dermatoses quite frequently– Pemphigus– Pemphigoid– Vasculitis– Connective tissue disease (lupus, DM)– Pyoderma gangrenosum– Lichen planus

• Higher doses, longer duration, more monitoring for side effects

• HPA axis suppression– Steroid withdrawal– Addisonian cris is

• Metabolic Effects– Hyperglycemia– Increased appetite– Hypertension– Cushingoid changes– Weight gain

• Bone– Osteoporosis– Osteonecrosis

• GI– Ulcers– Bowel perforation– Fatty liver

• Ocular– Cataracts– Glaucoma– Infection

• Psychiatric– Psychosis– Agitation– Personality change– Depression

• Neurologic– Pseudotumor– Neuropathy

• Infectious– TB reactivation– Fungal disease

• Muscular

Side effects

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Caution• Use caution in starting steroids for patients

with history of:– diabetes– hypertension– psychiatric disease– osteoporosis– gastric ulcer– chronic infections (eg. TB, systemic fungal)

Steroid sparing agents

• Methotrexate• Mycophenelate Mofetil• Azathioprine• Cyclosporine

Seborrheic Dermatitis

• Common, 2-5% of population, M and F• Commonly Called “Dandruff”

– Erythematous patches and plaques with overlying yellowish dry or greasy scales.

– Commonly over oil producing areas such as scalp, eyebrows, nasolabial folds, chest / sternal area (sebaceous glands)

Seborrheic Dermatitis Treatment• Shampoo as scalp and face wash

– Zinc pyrathione– Selenium sulfide– Ketoconazole

• Creams– Ketoconazole cream BID to affected areas, or– Sodium sulfacetamide BID– If erythema is a significant component, consider

HC 2.5% cream BID PRN (short duration)

Approach to Dermatologic Conditions

AcneInfectious diseases of the SkinEczemaPsoriasisSun Damage / Actinic Keratoses

Psoriasis Vulgaris

• Common, 1-2% of general population• Round, well-demarcated, dry, scaly

papules and plaques • Scalp, nails, extensor surfaces of the

limbs, umbilicus, and sacral region.

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Psoriasis Treatment• Topical Steroids• Topical Vitamin D analogues• UV light• Methotrexate• Retinoids• Biologics

Vitamin D analogues

• Calcipotriene– Comparable to potent topical steroids at 8 weeks

of treatment– Applied twice daily– May be used in combination with topical steroids,

often ‘in-regimen’– Can cause hypercalcemia

• Recommended application is 100g/week or less

Methotrexate• Inhibitor of dihydrofolate reductase and thymidylate

synthetase à blocks DNA synthesis (S phase specific)• Ultimate action is to inhibit cell division

MOA (psoriasis):– Blocks migration of T cells– Decreased proliferation of lymphocytes– Immunosuppression

Methotrexate• MANY SE’s, but well known, including but not limited to:

– GI – Oral ulcers– Liver toxic ity– Myelosuppression– Radiation recall– Pneumonitis– Pulmonary fibrosis– Infertility– Abortion

• Required meticulous lab monitoring before and during therapy• Folate 1mg qd• Start with test dose of 2.5mg before increasing to target• METHOTREXATE IS A Q WEEK DRUG!!!!

Cyclosporine

• MOA not fully understood, but involves:– Decreased T cell proliferation– Inhibition of pro-inflammatory cytokines

• FDA approved for psoriasis• Requires meticulous lab and BP monitoring• Weight based dosing, with short term (3-6

months) use ideal

Cyclosporine SE• Varied and many, including:

– Renal dysfunction– Hypertension– Headache– Hypertrichosis– Gingival hyperplasia– Nausea– Diarrhea– Myalgia– Hyperkalemia– Hypomagnesemia– Hyperlipidemia

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• Oral retinoid• Like all retinoids, acts

to normalize epithelial differentiation and keratinization

• Dosed orally• Requires meticulous lab monitoring before and during treatment

• Generally not given to women of childbearing potential– Two negative pregnancy tests

before initiation– Pregnancy prevention

• Limit alcohol use during treatment– Long lasting (years) metabolite

produced• No blood donation during

treatment and for 3 years after

Acitretin • Common SEs:– dry skin/mucous membranes – alopecia (50-75%) – cheilitis – peeling skin/sticky skin/fragile nails– decreased night vision – Joint aches– Photosensitivity

• SERIOUS SEs– elevated liver transaminases – pancreatitis – pseudotumor cerebri – hypertriglyceridemia/hypercholesterolemia, decreased HDL – depression (aggressive feelings or thoughts of self-harm)– Teratogenicity– IBD flare

Biologics• TNF alpha modulation

– Certolizumab (Cimzia)– Etanercept (Enbrel)– Adalimumab (Humira)– Remicade (Infliximab)* - IV Infusion– Golimumab (Simponi)

• IL12/23 modulation– Ustekinumab (Stelara)* - In-office injection

• IL-17 modulation– Secukinumab (Cosentyx)– Ixekizumab (Talz)

Biologics• Increase risk of infection

• Common SE– Respiratory infection– Flu-like illness– Injection site reaction

• Serious SE– Nervous system disorders– Cancer (lymphoma)– Blood dyscrasia– Reactivation of past infections (Hepatitis, TB, Fungal)

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Apremilast

• Inhibits phosphodiesterase 4 (PDE4) enzyme• Orally dosed

– Starts at 30 mg, titrates to 30 mg BID• SE:

– Diarrhea– Nausea– Headache – Weight loss

Approach to Dermatologic Conditions

AcneInfectious diseases of the SkinEczemaPsoriasisSun Damage / Actinic Keratoses

5-fluorouracil

• Antimetabolite• Use 5% cream BID for 2 weeks• Patients may use triamcinolone 0.1%

ointment bid during the last 5 days to help relieve the irritation

• Warn the patients! They will look terrible when it starts working – show them the pictures!

www.seton.net/derm